MHC class I molecules are key in immunity to viral infections as they present viral pep-tides to cytotoxic T lymphocytes. One of the hallmarks of MHC class I genes in outbred populations is their extraordinary polymorphism, yet the significance of this diversity is poorly understood. Cer-tain species with reduced MHC class I diversity, such as the cotton-top tamarin, are more susceptible to fatal virus infections. To explore the relationship between this primate's limited MHC class I diversity and its susceptibility to viruses, we infected five cotton-top tamarins with influenza virus. RESULTS Every tamarin recognized the same immunodominant CTL epitope of the influenza nucleoprotein. This nucleoprotein peptide was bound by Saoe-G*08, an MHC class I molecule ex-pressed by every cotton-top tamarin. Two tamarins also made a subdominant response to an epitope of the matrix (M1) protein. This peptide appeared to be bound by another common MHC class I molecule. With the exception of an additional subdominant response to the polymerase (PB2) protein in one individual, no other influenza-specific CTL responses were detected. In populations or species with limited MHC class I polymorphism like the cotton-top tamarin, a dependence on shared MHC class I molecules may enhance susceptibility to viral infection, since viruses that evade MHC class I-restricted recognition in one individual will likely evade recognition in the majority of individuals. OBJECTIVE: To explore the relationship between the cotton-top tamarin's limited MHC class I diversity and its susceptibility to viruses. FUTURE DIRECTIONS Further study possible reason for tamarin's unique susceptibility to viruses. KEY WORDS tamarin, MHC, CTL